Methods and compositions for targeting the vasculature of solid tumors

Abstract

The present invention relates generally to methods and compositions for targeting the vasculature of solid tumors using immunological- and growth factor-based reagents. In particular aspects, antibodies carrying diagnostic or therapeutic agents are targeted to the vasculature of solid tumor masses through recognition of tumor vasculature-associated antigens, such as, for example, through endoglin binding, or through the specific induction of endothelial cell surface antigens on vascular endothelial cells in solid tumors.

What is claimed is: 
     
       1. A method for treating a vascularized tumor, comprising administering to an animal having a vascularized tumor a biologically effective amount of a conjugate comprising a selected therapeutic agent linked to an antibody that binds to a complex of a growth factor and a growth factor receptor present on the surface of intratumoral blood vessels of the vascularized tumor, but that does not bind to the individual growth factor or growth factor receptor. 
     
     
       2. The method of claim 1, wherein the conjugate comprises a monoclonal antibody or monoclonal antibody fragment. 
     
     
       3. The method of claim 1, wherein the antibody binds to the same epitope as the monoclonal antibody GV39 (ATCC HB-12450). 
     
     
       4. The method of claim 1, wherein the antibody binds to the same epitope as the monoclonal antibody GV97 (ATCC HB-12451). 
     
     
       5. The method of claim 1, wherein the antibody binds to a complex of FGF and an FGF receptor. 
     
     
       6. The method of claim 1 wherein the antibody binds to a complex of TGFβ and a TGFβ receptor. 
     
     
       7. The method of claim 1, wherein the therapeutic agent is an anticellular agent capable of killing or suppressing the growth or cell division of tumor-associated endothelial cells of intratumoral blood vessels. 
     
     
       8. The method of claim 7, wherein the anticellular agent is a chemotherapeutic agent, a radioisotope, or a cytotoxin. 
     
     
       9. The method of claim 8, wherein the anticellular agent is a steroid, a cytokine, an antimetabolite, an anthracycline, a vinca alkaloid, an antibiotic, an alkylating agent, or an epipodophyllotoxin. 
     
     
       10. The method of claim 8, wherein the anticellular agent comprises a plant-, fungus- or bacteria-derived toxin. 
     
     
       11. The method of claim 10 wherein the toxin comprises an A chain toxin, a ribosome inactivating protein, α-sarcin, aspergillin, restrictocin, a ribonuclease, diphtheria toxins Pseudomonas exotoxin, bacterial endotoxin or the lipid A moiety of bacterial endotoxin. 
     
     
       12. The method of claim 11 wherein the toxin comprises deglycosylated ricin A chain. 
     
     
       13. The method of claim 1, wherein the antibody binds to a complex of a growth factor and a growth factor receptor, the presence of which on the intratumoral blood vessels is cytokine-inducible. 
     
     
       14. The method of claim 1, further comprising administering an antitumor antibody-therapeutic agent conjugate to the animal. 
     
     
       15. The method of claim 14 wherein the antitumor antibody-therapeutic agent conjugate comprises an HMFG-2, SM-3, B72.3, PR5C5, PR4D2, 9.2.27, OV-TL3, MOv18 or anti-p185 HER2  antitumor antibody or fragment thereof. 
     
     
       16. The method of claim 1, wherein the animal is a human cancer patient.